We propose to develop a dynamic quantitative phase-imaging interference 4D microscope system operating in reflection to enable creating phase image movies and quantifying motion of live cells and cellular processes in vitro without the need for adding contrast agents, ultimately having application to clinical measurements in vivo. The primary use of this microscope is to study the structure and mechanics of cells, cellular processes and tissues. This interference microscope will enable looking at cellular morphology, cellular development and structures within cells and tissues over periods of time. It is intended to have a flexible design that enables options of different magnifications, resolutions, and wavelengths. The Phase I project focuses on development of a dynamic polarization Michelson interference microscope with a 10-20X objective providing an optical resolution of 2.0 5m. Polarization states will be used to differentiate object and reference beams. Technology originally developed for dynamically measuring the seeing quality of large telescopes in situ will be utilized for imaging on the microscopic level. This technology utilizes a pixilated single-shot phase-measurement camera to enable instantaneous quantitative determination of optical phase and refractive index variations in real time to create movies of dynamic motions. Goals for Phase I include design of a modular polarization microscope and Michelson interferometer with the integrated pixilated phase-measurement camera, development of basic software algorithms to extract and create topographic and optical thickness movies of biological objects, testing the optical performance of the system and demonstrating dynamic 4D measurements on a number of in vitro cell cultures. PUBLIC HEALTH RELEVANCE: This dynamic quantitative phase-imaging technology implemented within an interferometric microscope system represents a key element in advancing the ability to image tissues, cells, and cellular components in real-time without the need for toxic contrasts agents to observe the motion and growth of cells in living biological objects, and discern differences between types of cells. This instrument will create dynamic 4D phase image movies of cellular events for studying in vitro cellular structure and morphology, motion, motility and mechanics.